Viola Brugnatelli & Fabio Turco have written „Principles of Clinical Cannabinology Handbook“. The book was published by CannabiScientia and Prohibition Partners. Below krautinvest.de presents to the readers: Chapter 2.9 Insight: Not only cannabinoids, the link between tryptophan and cannabis . More Infos: https://cannabiscientia.com/handbook/
By Viola Brugnatelli & Fabio Turco
Research carried out in 2022 identified two non-cannabinoid compounds not usually found in plants -kinurenic acid and L-kinurein-, products of tryptophan metabolism, which possess interesting neuromodulatory and other properties.
Tryptophan metabolism in animals and plants
Plants and animals share many biochemical pathways, but certain synthesis and catabolism (degradation) processes occur differently in the two kingdoms.
One example is the L-tryptophan metabolic pathway. Unlike plants, animals – particularly mammals and therefore humans – are unable to biosynthesise this essential amino acid, so they generally assimilate it through the diet.
In addition to being a constituent of all proteins in an organism, tryptophan is a metabolic intermediate involved in numerous processes of great biological importance.
Animals need to consume tryptophan through their diet. Foods particularly rich in tryptophan are:
- meat (especially chicken and turkey)
- fish (especially anchovy, sea bream, sea bass, sole, cod, tuna)
- vegetables (endive, cabbage, asparagus, green beans, lettuce, chard, spinach, courgettes)
- dark chocolate
- pine nuts
- sesame seeds
- milk and dairy products
Tryptophan in the human brain and, more generally, in the mammalian brain, is the biological precursor of several important molecules, such as the neurotransmitter serotonin (5-hydroxytryptamine, 5-HT), which is, in turn, the precursor of the neurohormone melatonin. The greater the amount of tryptophan-rich protein consumed in the diet, the greater the production of serotonin and melatonin.
Only a small fraction of tryptophan is converted to serotonin in animals, while a larger portion (about 95 per cent) of this amino acid is metabolised to L-kinurenine (KYN), which is further degraded to kynurenic acid (KYNA), an NMDA receptor antagonist with a protective function, or to 3-hydroxyquinurenine. The formation of KYNA and 3-hydroxyquinurenine represent the initial steps in the biosynthesis process of nicotinic acid, nicotinamide and B-complex vitamins.
KYN is a molecule with neuromodulatory action, which targets the aryl hydrocarbon receptor. KYN is a crucial factor in the regulation of the immune response.
In plants, the biochemical processes involved in tryptophan metabolism are different from those in animals.
Firstly, plants are able to self-synthesise tryptophan, but, as such, its content is relatively low. For the most part, tryptophan is incorporated into amino acid chains during the process of protein biosynthesis.
A smaller amount is converted into biologically important secondary metabolites, one of which is indolacetic acid, involved in plant growth regulation.
Although the kynurenine pathway is not one of the prevalent metabolic pathways, low amounts of KYN and KYNA have been reported in some plants and plant foodstuffs.
These two metabolites have been identified in some plants, such as:
- medicinal herbs (Taraxacum officinale, Urtica dioica, Chelidoniummajus)
However, it has not yet been established whether all plants are able to biosynthesise these metabolites or rather are produced by soil microorganisms and absorbed through the roots.
Regardless of the plant’s ability to produce KYN and its metabolites, their specific function has not yet been clarified.
- KYN and KYNA: two human neuromodulators identified in the Cannabis Sativa L.
Cannabis has attracted a great deal of attention in the last decade, thanks to the identification of several organic molecules with interesting pharmacological and nutraceutical properties.
Research on the molecular profile of cannabis has mainly focused on characterising the phytocannabinome (phytocannabinoid pool) of plant extracts. Other compounds that have attracted attention are polar molecules such as terpenes, the volatile component of cannabis and fatty acids.
In a paper published in the Journal of Pharmaceutical and Biomedical Analysis, researchers at the University of Modena and Reggio Emilia, Italy, under the leadership of Professor Giuseppe Cannazza, were also able to shed light on the presence of small secondary metabolites, such as those of the tryptophan pathway.
The researchers analysed the presence of tryptophan and its metabolites in various parts of plants grown both in soil and hydroponics.
Thanks to ultra-high-performance liquid chromatography, coupled with the high-resolution mass spectrometry platform (UHPLC-HRMS) normally used for metabolomic analyses, it was possible to detect compounds expressed even in very low quantities, including tryptophan and its metabolites KYN and KYNA.
To assess the distribution of these compounds in the different organs of the Cannabis Sativa L plant, roots, stem and leaves were collected from open-field cultivations at two different growth stages, corresponding to 30 and 90 days after germination, respectively, as well as in hydroponics.
The results obtained in soil cultivation suggested an increasing level of tryptophan, KYN and KYNA starting from the base (roots) and arriving at the top (leaves) of the plant, both at 30 and 90 days.
The results of extracts obtained from plants grown hydroponically also showed the presence of all analytes, with varying concentrations and trends similar to those observed for soil cultivation.
For both soil and hydroponics crops, the highest amounts of KYN and KYNA were found in the leaves.
Cannabis cultivation is attracting increasing interest, both medically and industrially. For these reasons, it would be of considerable interest to identify all the factors that regulate the plant’s growth and metabolism.
With this work, researchers have uncovered the presence of the important tryptophan metabolic pathway and its metabolites. In particular, the researchers identified the presence of kineuretic acid (KYNA) and L-kinurein (KYN) in leaves.
KYNA, in particular, is a molecule that has attracted a great deal of attention for its important pharmacological properties:
Furthermore, a hypolipidemic effect and cardiovascular protective function have recently been attributed to KYNA, suggesting a potential role as a functional food ingredient for the treatment of obesity and hyperlipidaemia and for modulating the gut microbiota.
The results obtained by Italian researchers suggest that Cannabis Sativa L may be a valuable source of TRP, KYN and KYNA.
Results, however, to be confirmed with further studies ‚to assess whether the concentrations of KYNA in cannabis leaf extracts used as cosmetics or nutraceuticals are sufficient to exert the numerous pharmacological activities attributed to this metabolite‘, as stated by the researchers themselves in the conclusion of their work.
Fabiana Russo, Francesco Tolomeo, Maria Angela Vandelli, Giuseppe Biagini, Roberta Paris, Flavia Fulvio, Aldo Lagan, Anna Laura Capriotti, Luigi Carbone, Giuseppe Gigli, Giuseppe Cannazza, Cinzia Citti.
Kynurenine and kynurenic acid: Two human neuromodulators found in Cannabis sativa L.
J Pharm Biomed Anal. 2022 Mar 20;211:114636.